Methods and systems for treating the gastrointestinal tract

ABSTRACT

The specification discloses methods and devices for electrically stimulating one or more structures in the gastrointestinal tract. The one or more structures are preferably selected from the upper esophageal sphincter, the esophagus and gastric fundus. The method may involve the step of arranging a plurality of stimulating electrodes adjacent one or more structures which may further include the lower esophageal sphincter, the stomach, the pyloric sphincter, the small intestine, the colon and the vagus. The method and device may further include sensing electrodes to detect change in one or more physiological parameters in the gastrointestinal tract and modulate the stimulating electrodes in response to the change. The device comprises a pulse generator, a power source, a plurality of stimulating electrode set, one or more sensing electrodes and means for varying activity of the stimulating electrodes in response to change detected in the gastrointestinal tract. The method and device may be used to treat obesity and/or GERD.

CROSS-REFERENCE

The present application is a continuation of U.S. patent applicationSer. No. 12/775,436, filed on May 6, 2010, which is a continuation ofU.S. patent application Ser. No. 11/539,645, filed on Oct. 9, 2006 andissued as U.S. Pat. No. 7,738,961.”

FIELD

This specification discloses methods and apparatuses for the electricalstimulation of selected gastrointestinal muscle or muscles. Moreparticularly, the disclosed inventions relate to methods and apparatusesfor the electrical stimulation of one or more portions of thegastrointestinal tract to increase muscle tone and/or induce musclespasm in the portion or to stimulate one or more nerves. The initiationor duration of the electrical stimulation may be modified by changes inphysiological parameters which may be monitored by the invention. Theinventions are particularly suited to decreasing caloric intake ordecreasing the tendency to caloric intake, thereby providing a means ofweight control.

BACKGROUND

It is generally known that obesity is a common condition and a majorpublic health problem in developed nations, including the United Statesof America. Today, 64.5% of American adults, about 127 million people,are either overweight or obese. Data demonstrated 300,000 Americans dieprematurely from obesity related complications each year. More than 25%of children today are overweight or obese in the United States ofAmerica, hence the number of overweight Americans has increased steadilyand will continue to increase in the coming years. Obesity costs theUnited States an estimated $100 billion annually in direct and indirecthealth care expenses and in lost productivity. This trend is alsoapparent in many other developed countries.

Morbid obesity is defined as more than 100 pounds greater than normalbody weight or a body mass index (BMI), greater than 40 kg/m.sup.2 andis present in 5% of the U.S. population. A BMI greater than 30kg/m.sup.2 is associated with significant co-morbidities. Morbid obesityis associated with many diseases and disorders, including diabetes,hypertension, heart attacks, strokes, dyslipidemia, sleep apnea,Pickwickian Syndrome, asthma, lower back and disc disease,weight-bearing osteo-arthritis of the hips, knees, ankles and feet,thrombophlebitis and pulmonary emboli, intertriginous dermatitis,urinary stress incontinence, gastro esophageal reflux disease (GERD),gall stones, and sclerosis and carcinoma of the liver. In women,infertility, cancer of the uterus and cancer of the breast are alsoassociated with morbid obesity. Taken together, the diseases associatedwith morbid obesity markedly reduce the odds of attaining an averagelifespan and raise annual mortality in affected people by a factor of 10or more.

Current treatments for obesity include diet, exercise, behavioraltreatments, medications, surgery (open and laproscopic) and endoscopicdevices. There are currently three (3) weight loss drugs approved by theU.S. Food and Drug Administration. Orlistat (XENICAL™) provided by Rocheis a non-systemic inhibitor of the enzyme lipase that works byinterrupting the action of lipase in breaking down fats. Sibutraminehydrochloride (MERIDA™) is a non-amphetamine appetite suppressant thatinhibits brain chemicals involved in appetite, thereby promoting asignal of satiety. Phentermine (ADIPEX-P™) is a structural analog ofamphetamine and is also an appetite suppressant indicated for exogenousobesity.

In addition, there are currently a number of clinical trials on-goingfor treatments of obesity. One line of enquiry is based around thechemistry of the hormone called Human Amylin, which plays a role in theregulation of appetite and food intake. Mid-stage clinical trial resultswith one of these products have shown a weight loss of 3.5 kg (7.7 lbs)over 60 weeks. While these drugs have shown signs of greater efficacy,there has not been developed any high efficacy pharmaceutical treatment.Further, the issue of short-term and long-term side effects is always ofconcern to consumers, pharmaceutical providers and their insurers.

Laporoscopic bariatric surgical procedures in current use includeLaporoscopic V or vertical gastroplasty, laporoscopic gastric bypasswith Roux Y Limb and a Laporoscopic Placement of Lap Band. Theseprocedures have been reported to result in marked lasting weightreduction in the majority of morbidly obese patients when assessed fiveyears after operation. Studies of the health-related quality of lifeoutcomes of these procedures have documented sustained significantimprovements in all parameters measured. Diet or drug therapy programshave been consistency disappointing and fail to bring about significant,sustained weight loss in the majority of morbidly obese people.

Currently, most (95%) morbid obesity operations are, or include, gastricrestrictive procedures, involving the creation of a small (15-35 ml)upper gastric pouch that drains through a small outlet (0.75-1.2 cm),setting in motion the body's satiety mechanism. About 15% of morbidobesity operations done in the United States involve gastric restrictivesurgery combined with a malabsorptive procedure. This divides smallintestinal flow into a biliary-pancreatic conduit and a food conduit.Potential long-term problems with surgical procedures are notorious andinclude not only those seen after any abdominal procedure, such asventral hernia and small bowel obstruction, but also those specific tobariatric procedures such as gastric outlet obstruction, marginalulceration, protein malnutrition and vitamin deficiency.

Additionally, there are in development multiple endoscopic proceduresfor obesity. Endoscopically placed gastric balloons restrict the gastricvolume and result in satiety with smaller meals. Endoscopic proceduresand devices to produce gastric pouch and gastrojejunal anastomosis toreplicate laporoscopic procedures are also in development. Theseprocedures, however, are not without their risks.

Gastric electric stimulation (GES) is another procedure that iscurrently in clinical trial. Gastric Electrical Stimulation (GES)employs an implantable, pacemaker-like device to deliver low-levelelectrical stimulation to the stomach.

The procedure involves the surgeon suturing electrical leads to theouter lining of the stomach wall. The leads are then connected to thedevice, which is implanted just under the skin in the abdomen. Using anexternal programmer that communicates with the device, the surgeonestablishes the level of electrical stimulation appropriate for thepatient.

While the exact way in which GES causes weight loss is not fullyunderstood, it is believed that through low-level electrical pulses thetherapy slows the intrinsic electrical waves in the stomach. Animalstudies have shown that this electrical stimulation causes the stomachto relax, resulting in distension of the stomach. This distensiontriggers nerves in the stomach involved in digestion to send signals viathe central nervous system to the brain that the stomach is “full”.

GES may also result in a decrease in gastro-intestinal hormones such asCCK, somatostatin GLP-1 and leptin, all of which are associated withhunger. Recent work on GES has shown promising results in obesepatients. GES results in 35% EWL (excess weight loss) beyond 24 monthsand the results are sustained and replicated. This technology iscurrently available in Europe and Canada and undergoing trials for FDAapproval in the U.S

U.S. Pat. No. 6,901,295 to the present applicant describes a method andapparatus for electrical stimulation of the lower esophageal sphincter(LES). The device and method are directed toward inducing contraction ofthe LES to thereby combat gastro esophageal reflux disease (GERD). Theclaimed invention is directed towards using, amongst other things,sensing electrodes in the esophagus for detecting esophageal peristalsisso as to inhibit the electrical stimulation of the lower esophagealsphincter in order to pass food to the stomach. The disclosed device andmethod, therefore, increases LES tone after passage of food to thestomach. It is designed to prevent gastric reflux of acid material.

Published US Patent Application No 2005/0065571 to Imran discloses aresponsive gastric stimulator which senses one or more parameters andthen affects smooth muscle contractions and nerves associated with thestomach and/or biochemistry or secretions of the stomach. Stimulationmay be directed to cause gastric retention of food for a greaterduration by interfering with peristaltic contractions and/or the innateelectrical potentials of the stomach.

Published US Patent Application No 2005/0090873 to Imran discloses afixation device for holding stimulating electrodes in electrical contactwith the wall of a portion of the gastrointestinal tract. This devicecomprises an expandable member that fixes electrodes in electricalcontact with the gastrointestinal tract. The disclosure also extends toa method for treating obesity by controlling the pylorus to retain foodin the stomach for a desired period of time to provide a sensation ofsatiety and/or to reduce hunger. The disclosed invention is relativelycumbersome and involves the intra-luminal insertion of an expandablemember that presents some degree of risk in the duodenum. Food must beable to pass through the device while at the same time its expansivepressure must be sufficient to hold electrodes in place, but not damagethe wall of the small intestine. The method and device also seek tocontrol contraction of the pylorus by electrical stimulation of theduodenum.

Published US Patent Application No 2003/0144708 to Starkebaum relates toa method and system for treating patients with eating disorders,including obesity, through the delivery of electrical stimulationdirectly or indirectly to the pylorus of a patient to close the pyloriclumen to inhibit emptying of the stomach.

Published US Patent Application No 200410015201 to Greenstein disclosesa process for electro-stimulation treatment of obesity. This disclosureis directed to electro-stimulation of the stomach, the lower esophagealsphincter, the pyloric sphincter and the ileo-caecal sphincter.

International Publication No WO20051051486 to University TechnologiesInternational Inc. discloses a method and apparatus for gastrointestinalmotility control. This discloses a complex multi-channel implantabledevice using one or multiple micro-system controlled channels andcircumferentially arranged sets of two more electrodes to provideexternally-invoked synchronized electrical signals to the smooth musclesvia the neural pathways. The applicant describes invoking peristalsisbut also corrupting peristalsis by implanting electrodes in the pyloricregion or other areas of the stomach. The claimed invention relates toelectrically-stimulating patches in the vicinity of an organ until theorgan relaxes and applying electrical energy to the gastrointestinaltract to invoke a desired motility result. The identified specificationdoes not disclose any means of feedback.

U.S. Pat. No. 6,611,715 to Boveja describes an apparatus and method fortreating obesity and compulsive eating disorders using an implantablelever receiver and an external stimulator. The lead-receiver is inelectrical contact with the left vagus nerve. The device is used forneuromodulating the vagus nerve with a result of appetite suppression.

SUMMARY

It is an object of the present invention to provide a method andapparatus for increasing UES, esophageal or LES sphincter tone todecrease or delay esophageal emptying. The present invention may alsoextend to delaying emptying of the stomach and increasing satiety in asubject.

It is an object of the present invention to provide a method andapparatus for increasing UES, esophagus or LES tone to decrease or delayesophageal emptying.

It is also an object of the present invention to provide a method andapparatus for preventing or limiting esophageal emptying by increasingUES, esophageal or LES tone without causing permanent injury to thesurrounding tissue or organs.

It is a further object of the present invention to provide a method andapparatus for preventing or restricting esophageal emptying byincreasing UES, esophageal or lower esophageal or LES tone that isvariable by changing the duration, power and frequency of stimuliwithout requiring subsequent endoscopic surgical or radiologicalprocedures.

It is a still further object of the present invention to provide amethod and apparatus for treating obesity by providing electricalstimulation to the UES, esophagus or LES or nerves supplying thestructures through the use of one or more electrodes. The method andapparatus may be supplemented by further including stimulation of thestomach, and/or pylorus.

It is another object of the present invention to provide a method andapparatus for the stimulation of the gastric fundus to interfere withreceptive relaxation and/or gastric accommodation to induce satiety.

It is a further object of the present invention to monitor physiologicalparameters and to modulate electrical stimulation according to changesin those parameters.

It is also an object of the present invention to provide a method andapparatus of preventing or limiting pyloric relaxation only in responseto a nutrient rich meal.

It is a further object of the present invention to apply any of theabove methods in combination with stimulation of the vagal nerve, smallintestine, or colon.

In a first broad aspect, the invention resides in a method of modifyingactivity of the gastrointestinal tract in a subject.

A method of modifying activity of the gastrointestinal tract in asubject including the steps of electrically stimulating one or both ofthe upper esophageal sphincter and the esophagus to induce contractionof smooth muscle therein. The method may further comprise the step ofelectrically stimulating one or more of the LES, the stomach and thepyloric sphincter as well as, optionally, stimulating the vagus nerve,small intestine or colon.

In a further aspect, the invention may reside in a method ofelectrically stimulating one or more structures in the gastrointestinaltract to increase muscle tone by arranging a plurality of stimulatingelectrodes within or adjacent a portion of the gastrointestinal tract sothat electrical stimuli causes the one of more structures to contractand wherein the structure is the UES and/or the esophagus. The methodmay further incorporate the step of placing a plurality of stimulatingelectrodes in communication with LES, the stomach and/or the pyloricsphincter; small intestine or the colon wherein electrical stimuli fromthe stimulating electrodes causes the respective structure to contract.The method may include the step of stimulating the vagus.

In yet a further aspect, the invention may reside in a method ofelectrically stimulating one or more structures in the gastrointestinaltract by:

arranging a plurality of stimulating electrodes within a portion of thegastrointestinal tract;

providing electrical energy to the stimulating electrodes to therebycause the structure to be stimulated;

arranging one or more sensing electrodes to detect change inphysiological parameters in the blood or the gastrointestinal tract andmodulating the stimulating electrodes in response to the change detectedin the blood or the gastrointestinal tract to modify operation of theone or more structures.

The method may preferably relate to the UES, the esophagus, the LESand/or the vagus. The one or more structures may further include thestomach and/or the pyloric sphincter, small intestine or the colon.

The one or more physiological parameters may include esophagealperistalsis, esophageal pH, esophageal impedence, esophageal electricalactivity, gastric peristalsis, gastric electrical activity, gastricchemical activity, intra-gastric temperature, pH or impedence; bloodchemical and hormonal activity; vagal electrical or chemical activity.

One or more sensing electrodes may be positioned in one or more of theesophagus, the stomach the small intestine, colon, vagus or patientsvascular system.

In yet a further aspect, the invention may reside in a device forelectrical stimulation of a structure in the gastrointestinal tractwherein the device includes:

a pulse generator;

a plurality of stimulating electrode sets connected through wires orwirelessly to the pulse generator and adapted to be positioned within oradjacent the structure or in contact with nerves innovating thestructure; and

one or more sensing electrodes for monitoring physiological parameters;and

means for varying activity of the stimulating electrodes in response tochange detected in the physiological parameters to thereby modifyoperation of the structure.

The means for varying activity may be a microprocessor device andpreferably also includes a power source. The structure may be one ormore of the UES, the esophagus, the LES, the stomach, the pyloricsphincter the vagus, the small intestine and the colon. The shape of theelectrical stimulation may be any suitable shape, preferably sinusoidal,square, rectangular or saw-toothed. The frequency of stimulation ispreferably in the range of 1 Hz-1 MHz. The pulse generator may beconnected to the electrode sets by wires or wirelessly. The sensingelectrodes may be connected to the microprocessor by wires orwirelessly. The device may also be turned on or off by the patient atappropriate time related to the meal.

The above method and device may be applied for the treatment of obesity.

It is a further object of the present invention to provide a method andapparatus for preventing or slowing esophageal emptying by increasingUES, esophageal or LES sphincter tone without causing permanent damageto the surrounding tissue or organs as well as optionally delayinggastric emptying and increasing sense of satiety. The present inventionmay also be used to treat GERD by stimulating the LES and/or theesophageus to prevent gastric reflux after eating.

BRIEF DESCRIPTION OF THE DRAWINGS

To enable the invention to be fully understood, reference will now bemade to the accompanying illustrations, in which:

FIG. 1 is a schematic illustration of a portion of the gastrointestinaltract;

FIG. 2 is a schematic representation of the device of the presentinvention with stimulating electrodes implanted in the upper esophagealsphincter;

FIG. 3 is a schematic representation of a device of the presentinvention with stimulating electrodes implanted in association with thevagus;

FIG. 4 is a schematic representation of a device of the presentinvention with stimulating electrodes implanted in the esophagus;

FIG. 5 is a schematic representation of the present invention withstimulating electrodes implanted in the lower esophageal sphincter;

FIG. 6 is a schematic representation of the present invention withstimulating electrodes implanted in the stomach;

FIG. 7 is a schematic representation of the present invention withstimulating electrodes implanted in the pylorus;

FIG. 8 is a schematic representation of the present invention withsensing electrodes in the stomach and stimulating electrodes in contactwith the vagus and the stomach; and

FIG. 9 is a schematic representation of one or more devices of thepresent invention with electrodes implanted in each of the upperesophageal sphincter, the esophagus, the lower esophageal sphincter, thestomach, the pylorus and the vagus.

DETAILED DESCRIPTION

Referring to FIG. 1, there is seen a portion of the gastrointestinal(GI) tract, including the upper esophageal sphincter (UES) 11, esophagus12, lower esophageal sphincter 14, stomach 15, pyloric sphincter 16 andduodenum 17. The UES 11 connects the oropharynx 18 and esophagus 12 andacts as a barrier to impede the passage of oral contents into theesophagus. The UES is contracted and therefore closed in a fasting stateand undergoes periods of relaxation during the feeding or swallowingphase so as to allow oral contents to pass into the esophagus.

The LES 14 connects the esophagus 12 to the stomach 15 and acts as abarrier to impede the passage of esophageal contents into the stomach.The LES also acts to prevent regurgitation of stomach acid contents intothe lower esophagus. The LES is contracted in a fasting state andundergoes periods of relaxation during the feeding or swallowing phaseso as to allow the esophageal contents to pass into the stomach. The LESis a smooth muscle.

LES spasm or non-relaxation results in delayed esophageal emptyingwhich, in turn, results in difficulty swallowing, early satiety and aresultant weight loss.

The pyloric sphincter 16 is located between the stomach and the duodenumand acts as a barrier to impede the passage of gastric contents from thestomach to the duodenum. The pyloric sphincter is in a contracted phasein the fasting state and undergoes periods of relaxation during thepost-feeding phase to allow gastric contents to flow from the stomachinto the duodenum 17.

The vagus or vagal nerve 13 is the dominant parasympathetic innervationto the upper G.I. and modulates perception and G.I. motor functions.Afferent vagal fibres from the stomach wall increase their firing ratewhen the stomach is filled with nutrients. Accordingly, extraphysiological electrical stimulation of the vagus nerve from just abovethe stomach level may produce appetite suppression, by causing a patientto experience satiety. The left vagus nerve is preferred for siting thepresent invention as it provides minimal innervation to thecardiopulmonary system and mainly innervates the visceral organs such asthe gastrointestinal tract. Stimulation of the left vagus nervetherefore can be expected not to cause any deleterious cardio pulmonaryside effects. The fundus 25 of the stomach normally relaxes in responseto a meal, thus allowing for accommodation of food bulk.

Referring to FIG. 2, there is seen a first embodiment of the presentinvention wherein a plurality of electrode sets 21 is placed in a looselinear configuration in the upper esophageal sphincter (UES). A pulsegenerator 20 is provided for stimulation of the electrodes andcorresponding portion of the G.I. tract. The pulse generator 20 isconnected to a power source 22 for supplying a source of power. Thepulse generator 20 is further connected to the electrode sets 21 bywires 23 for applying the electrical stimulus to the electrode sets 21.

Alternatively, the electrode sets 21 may be coupled to the pulsegenerator 20 in a wireless fashion using an RF link, an ultrasonic link,a thermal link, a magnetic link, an electromagnetic link or an opticallink. The power source 22 can be either a direct current source or analternating current source. The number of electrode sets is determinedby a number of factors, including the size of the electrodes, theirpower and the size of the desired placement area. Preferably, the pulsegenerator 20 is controlled by a microprocessor 24 for applying theelectrical stimulus for periods of variable duration and variablepower/frequency, so as to produce the preferred contraction orcontractions.

Sensing electrodes 28 may be located in the esophagus 12 andelectrically connected by wires 26 to the microprocessor 24.Alternatively, the sensing electrodes 24 may be in wirelesscommunication with the microprocessor. The sensing electrodes may beselected to sense one or more physiological parameters in the esophagus.The physical parameters may include esophageal peristalsis, pH,pressure, temperature and impedence. Upon sensing appropriate changes inesophageal peristalsis, pH, pressure, temperature and/or impedence, theelectrical stimulation in the upper esophageal sphincter may beinitiated so as to contract the upper esophageal sphincter and impedepassage of food from the oropharynx into the esophagus, therebyincreasing the time of mastication, reducing the food intake and,preferably, increasing stimulation of the satiety centre. Stimulation ofthe UES may occur in the absence of the sensing electrodes 28 and thedevice may comprise the pulse generator 20, power source 22,microprocessor 24, electrical sets 21 and the wires or optionally awireless arrangement. Stimulation of the UES may be timed to coincidewith eating and may even be controlled by an external control unit.

Referring to FIG. 3, there is seen a device 27 comprising a pulsegenerator 20, power source 22 and microprocessor 24 as previouslydescribed. The device 27 is in electrical connection, either by wire orwirelessly, with stimulating electrode sets 121 located on or incommunication with the vagus 13. Sensing electrodes 120 are incommunication with the microprocessor 24 by a wire 128 although,optionally, the connection may be wireless. The sensing electrodes inthis circumstance are positioned in the stomach and may be adapted tosense the status of one or more physiological parameters. Thephysiological parameters may include but are not limited to stomachacidity, peristalsis, impedence, pressure, temperature, tone andelectrical activity. Changes in the physiological parameters may bedetected by the microprocessor 24 with subsequent stimulation orcessation of stimulation of the vagus 13 through stimulating electrodes121. For example, a sensation of increased peristalsis and muscle toneor pH change may indicate the presence of food in the stomach 15,therefore leading to stimulation of the vagus 13 with consequentsensation of satiety in the subject.

FIG. 4 shows a device 27 as previously described comprising a pulsegenerator 20, power source 22 and microprocessor 24. A plurality ofelectrode sets 221 are placed in the esophagus 12, preferably in a looselinear configuration. Although shown as located in the proximal portionof the esophagus 12, the electrode sets may be positioned as preferredfor ease of access, placement and operation. The electrodes 221 and thepulse generator are in wireless communication. Sensing electrodes 228are shown in this case with one in the esophagus and one in the stomach.The sensing electrodes are adapted to determine physiologicalparameters, such as are described above. The sensing electrodes 228 arein communication with the microprocessor 24 by wires 26 but mayoptionally be in wireless communication.

In one embodiment, the device 27 does not include sensing electrodes andis simply a stimulating arrangement for stimulating the smooth muscle ofthe esophagus 12 to contract as required. Contraction may he initiatedduring feeding times by the patient to limit the passage of food fromthe oropharynx 10 to the stomach 15, thereby stimulating the satietycentre or inducing a sensation of longer feeding in the patient. Thesensing electrodes may be sited as preferred and may be in theesophagus, in the stomach or at another appropriate anatomical region.

In FIG. 5 there is shown an embodiment of the present invention whereinthe device includes stimulating electrodes 321 placed in a loose linearpattern in or near the LES 14 and in communication with a pulsegenerator 20 connected via wires 23 or, optionally, in wirelesscommunication with the pulse generator 20. Stimulation of the electrodes321 causes contraction of the LES and, thereby, restricts entry of foodfrom the esophagus 12 into the stomach 15. It is preferred thatcontraction of the LES occurs during feeding. However, the presentinvention may also be used to treat GERD, during non-feeding times byinducing stimulation of the LES during non-feeding periods. The presentdevice therefore has considerable utility and versatility. This limitsentry of food into the stomach and thereby decreases overall caloricintake.

The device 27 preferably includes sensing electrodes 328 for determiningthe status of preferred physiological parameters and, either detectingchanges in the status or providing information to the microprocessor 24to determine changes. The function of all sensing electrodes may besimilar to this description. Changes indicative of feeding may inducestimulation of the stimulating electrodes 321 and cause contraction ofthe LES. Of course, it is possible to have the sensing electrodes in thesame region as the stimulating electrodes if preferred. In oneembodiment, the electrodes may include both a stimulating and sensingfunction.

In addition, the stimulating electrodes 321 can be programmed tostimulate the LES in response to changes in physiological parametersassociated with acid or non-acid reflux sensed by the sensing electrodes328 in order to treat obesity associated gastro-esophageal refluxdisease.

FIG. 6 shows a device 27 with a plurality of stimulating electrode sets421 positioned in the stomach 15. The device includes a pulse generator20, power source 22 and microprocessor 24 in communication with eachother. Sensing electrodes 428 are positioned in the stomach 15 and incommunication with the microprocessor 24. The sensing electrodes areformed as a plurality of electrode sets which are designed to detect oneor more preferred physiological parameters. Changes in the parametersmay be determined by the sensing electrodes and/or the microprocessor 24of the resultant stimulation as appropriate of the fundus 25 via theplurality of electrode sets 421. For example, the stimulation of thesensing electrodes 428 by a drop in pH indicating secretion of stomachacid, or by increased peristalsis or by increased impedence may lead toactivation of the plurality of electrode sets 421 to cause contractionof the fundus 25 or disruption of normal receptive relaxation oraccommodation of the stomach, thereby inducing a decrease in food intakeand increased stimulation of the satiety centre.

In FIG. 7 a plurality of stimulating electrode sets 521 are implanted ator near the pylorus. Clearly, the electrode sets may be placed anywherewhere the action is such as to cause contraction of the pylorus and maybe proximal or distal thereto, provided the necessary activity isprovided. This also applies to other structures in this specification,it is to be understood that stimulation of a structure includesstimulation of nerves innervating that structure and electrodes may bepositioned accordingly. In this case, sensing electrodes 528 arepositioned in the upper esophagus/lower esophagus/stomach and are inwireless communication with the microprocessor 24. Stimulation of one ormore of the sensing electrodes 528 may cause stimulation of theplurality of electrode sets 521 located in the pylorus. Thisprecipitates contraction of the smooth muscle of the pyloric sphincter16 with resultant restriction of movement of food into the duodenum 17,delayed emptying of the stomach 15 and decreased caloric intake of thesubject.

The sensing and stimulating electrode sets may be placed in the mucosal,sub-mucosal, muscularis or serosal layer of the UES, esophagus, LES,stomach and pyloric sphincter and possibly duodenum. The electrode setsmay be placed by endoscopic, surgical or radiological procedures. Thestimulating electrodes may also be placed in operative relationship tothe vagus or colon.

Each of the stimulating electrode sets preferably provides an electricalstimulus of less than 1 amp. The electrical stimulus can be providedcontinuously or intermittently. For example, one time or more per hourmay be suitable in some circumstances. Over time, stimulation, whethercontinuous or intermittent, may serve to tone the smooth muscle of theUES, esophagus, LES, stomach or pylorus or other structure, withsufficient tone. Further electrical stimulation may be reduced oravoided. Depending on the patient, obesity may be successfully treatedwith a single treatment, or life-long stimulation may be required.

The electrical stimulus in the stimulating electrode sets may have anyshape necessary to produce the desired result, including a square,rectangular, sinusoidal or saw-tooth shape. The frequency of theelectrical stimulus is preferably in the range of approximately 1 Hz-1MHz. The stimulus may be triggered by a transmitter (not shown) externalto the body, similar to a remote transmitter for a cardiac pacemaker.With appropriate power settings and treatment periods, meal-induced UES,esophageal LES or pyloric relaxation is eliminated or minimized withoutcausing permanent injury to the surrounding tissue or organs. The extentof this activity is preferably modified by monitoring indicativephysiological characteristics. Objective measurement of the effects canbe made by physical examination, serum chemical analysis or with amanometery catheter to measure UES, esophageal muscle, LES, stomach orpyloric muscle tone and function or by using barium radiography orscintigraphy to measure esophageal or gastric emptying. The sensingelectrodes when included may be used to sense changes in esophageal orgastric pH, pressure, temperature, impedence due to feeding andthereafter appropriately modify (increase or decrease), the electricalstimulus. The sensing electrodes can be included on or in thestimulating electrode sets to sense changes in physiological parameterssuch as esophageal or gastric pH, pressure, temperature, impedence,electrical activity or changes in blood chemistry, or hormone levels dueto nutrients and appropriately modify increase or decrease of theelectrical stimulus.

Additional sensing electrodes may be placed in the esophagus to monitoresophageal peristalsis, pH, pressure, temperature, electrical activityand/or impedence. Upon sensing an appropriate change, electricalstimulation of the pylorus may be initiated so that the pylorus cancontract and impede passage of food from the stomach to the smallintestine. Control of the pylorus can also be achieved by turning on oroff the pulse generator. The stimulating electrode sets of thisinvention can be used in combination with additional pacing electrodes,as are known in the art, to treat disorders of acid reflux or gastricemptying or other gastrointestinal disorders.

In the preferred embodiments of the arrangement, there may be at leasttwo spaced sites at which a respective plurality of stimulatingelectrodes are located.

Referring to FIG. 8, there is seen a device 27 and a second device 27 a,both comprising pulse generator 20, power source 22 and microprocessor24 The two devices may be in communication with each other. One devicemay control more than one set of sensing and/or stimulating electrodes.

The first device 27 includes a plurality of stimulating electrodes 621positioned on or in proximity to the vagus 13. Sensing electrodes 628are positioned around the proximal stomach and LES. The electrode arraysmay combine both sensing and stimulating functions. Sensing informationis passed onto the microprocessor which is programmed to provide asuitable response to the pulse generator which in turn will stimulate orinhibit the stimulating electrode 621.

The second device 27A is in communication with a plurality ofstimulating electrodes 621A positioned in a loose-linear configurationin the fundus 25 of the stomach 15 so that stimulation of the electrodeswill cause contraction of the fundus of the stomach. The sensingelectrodes 628 may also be in communication with the second device 27Aand, in the present case, this would be via wireless communication. Theadvantage of the present invention becomes clearer in the presentarrangement as the microprocessors may be programmed to provide asophisticated response and a range of stimulation to the operativeelectrodes. Stimulation of the vagus 13 in tandem with delay of gastricaccommodation/receptive relaxation by stimulation of the electrodes 621Agives a double facet effect which, in some circumstances, may beaccumulative or even synergistic. This may result in the need for lessstimulation of the individual areas and less protracted stimulationbefore a permanent or extended benefit arises from the treatment.Although different devices 27, 27A are shown, it is clear that thecapacity in the device may be such that different location electrodes,stimulating or sensing, may be controlled by one arrangement of thepulse generator, microprocessor and power source. The complexities oflocation and safety considerations will dictate the preferredarrangement. It is envisaged that the present invention may extend toany two or more combinations of stimulating electrode sets in two ormore of the UES, the esophagus, the LES, the stomach, the pylorus, thesmall intestine, the colon and the vagus. Preferably, the effect ofthese arrangements are modulated by the presence of sensing electrodeswhich, again, may be in one or more multiple appropriate positions andadapted to sense the level or changes of physiological parameters suchas temperature, pH, impedence, muscle tone and intestinal wall motility,or electrical activity.

Referring to FIG. 9, there is seen a complex arrangement which covers anumber of the alternative configurations discussed above. While it isconsidered to be unlikely that any single patient would be subject toall these configurations, it is not impossible that it may be necessaryif the patient is sufficiently compromised and the clinical conditionrequires such an input. A device 27 is shown in with a pulse generator20, power source 22 and microprocessor 24. Wires 23 lead to a pluralityof stimulating electrode sets 21 in the UES 11. Wires 23A also lead to aplurality of stimulating electrode sets 21A in the esophagus 12. A thirdset of wires 23B leads to a plurality of stimulating electrode sets 21Bin the LES 14. All the stimulating sets may include sensing sets also incommunication with the device via the microprocessor 24 and, in thiscase, by wireless communication although information on physiologicalparameters may be passed through the pulse generator to themicroprocessor or through wired communication paths. A second device 27Awhich, in this case, is shown as a single encapsulated box alsoincorporates power supply, pulse generator and microprocessor aspreviously described which are not shown separately. Wires 23C connectto stimulating electrodes 21C. Sensing electrodes may be present andpositioned around the stimulating electrodes 21C. A third device 27B isshown with wires 23D in communication with stimulating electrodes 21D inthe stomach wall. A fourth device 27C is shown in communication withelectrodes 21E which are stimulating electrodes through wires 23E andmay include sensing electrodes proximal to the pylorus 16. A fifthdevice 27D is shown with electrodes 21F on or adjacent the pylorus 16,and a sixth device 27E is shown with electrodes 21G distal to thepylorus, but positioned to activate the pylorus. A seventh device 27F isshown with electrodes 21H positioned adjacent the lower greatercurvature of the stomach 15. Wire connections are shown for each butthey may be wireless.

An independent and eighth device 27G is shown with electrodes 21J on theesophagus 12 via wires 23J. A similar arrangement may be used in thesmall and/or large intestine.

A skilled addressee may choose the arrangement suitable for a patient.The arrangement may be independent devices or a single device withmultiple foci of electrodes either stimulating alone or in combinationwith sensing electrodes. The device can also be remotely turned on andoff by the patients or an appropriately designated person.

From the foregoing detailed description, it can be seen that the presentinvention provides an improved method and apparatus for electricalstimulation of one or more of the UES, esophagus, LES, stomach, pyloricsphincter, small intestine, colon and vagus.

Preferably, the stimulation is modulated in response to change detectedin the blood, the gastrointestinal tract or the nerves supplying thegastrointestinal tract. The change may be in physiological parameterssuch as esophageal peristalsis, gastric peristalsis, gastric electricalactivity, gastric chemical activity, intra-gastric temperature, musclewall tone and pH. The present invention is preferably achieved by theplacement of electrode sets in one or more of the UES, esophagus, LES,stomach, vagus or pyloric sphincter in an arrangement that inducescontractions of the UES, esophagus, LES, stomach or pyloric sphincter,due to electrical stimulation of the surrounding tissue and nerves orinduces a feeling of satiety by stimulation of the vagus. The electricalstimulation is preferably applied by a pulse generator for periods ofvariable duration and variable frequency, so as to produce the desiredcontraction.

It is notable that the UES, LES and pyloric sphincter are in acontracted phase in the fasting state and undergo periods of relaxationduring the fed phase so as to allow food bolus to pass from the mouthinto esophagus, stomach and the duodenum. In order to impede food fromreaching the duodenum, an electrical stimulus is applied to one or morelocations in the UES, esophagus, LES, stomach or the pyloric sphincter.These stimuli cause contraction of the UES, esophagus, LES, stomachand/or the pyloric sphincter and prevent or slow passage of a food bolusfrom the mouth to the duodenum. Alternatively or additionally,stimulation of the gastric fundus or vagus may increase the sensation ofsatiety and decrease caloric intake.

In particularly preferred embodiments, a plurality of electrode sets areplaced in the G.I. tract near the UES, esophagus, LES, stomach, pyloricsphincter, small intestine, colon or the vagus and preferably near twoor more. Each of the stimulating electrode sets may be comprised of atleast one active electrode and at least one ground electrode. Theelectrode sets may be arranged in any pattern that produces the desiredstimulation to the target region or structure and may include acircumferential pattern, a longitudinal axis, a regular pattern or otherplacement.

As used herein, the pyloric sphincter is a smooth muscle located betweenthe stomach and the small intestine, that acts as a barrier to emptyingof gastric contents into the small intestine. Pyloric relaxation allowsfor gastric contents to pass into the small intestine. Pyloric spasm ornon-relaxation results in delayed gastric emptying which, in turn,results in early satiety and weight loss.

The LES is a muscle at the end of the esophagus that regulates emptyingof esophageal content into the stomach. In addition, the LES alsoprevents reflux of gastric contents into the stomach. Esophagealemptying has been shown to be slowed and LES tone maintained bystimulating the LES to maintain it in the closed position, thusproducing LES spasm.

The present invention, therefore, allows a clinician to selectivelyprevent UES, esophagus, LES, stomach or pylorus, relaxation duringeating by stimulating one or more of the structures or nerves supplyingthe structures to thereby limit the intake of a patient.

The present invention may be used in a stimulating mode alone or inconjunction with sensing electrodes that sense physiological parametersand modulate the activation of stimulating electrodes. The physiologicalparameters may include esophageal peristalsis, esophageal pH orimpedence, esophageal electrical activity gastric peristalsis, gastricpH, gastric temperature, gastric impedence, gastric electrical orchemical activity, antro-pyloric impedence, blood chemical activity orgastro-intestinal neural activity.

The advantages of the present invention include the ability to preventpyloric relaxation only in response to, for example, a nutrient-richmeal which may be detected by changes in the physiological parameters.The present invention provides a relatively non-invasive andnon-surgical response to eating disorders and clinical conditions suchas obesity and related conditions.

Without being bound to any one theory, it appears direct stimulation ofthe gastric fundus may increase satiety by stimulating the gastricfundus and inhibiting gastric fundic receptive relaxation andaccommodation. Gastric fundic receptive relaxation and accommodationoccurs in response to meals and allows the stomach to accommodate themeals. Lack of gastric fundic receptive relaxation and accommodationresults in symptoms of fullness and early satiety.

The present invention generally uses conventional laproscopic,endoscopic radiological, or other minimally invasive surgical techniquesto place the desired device or devices on or adjacent to or incommunication with the structure with which it is to be associated.Conventional electrode stimulation devices may be used in the practiceof this invention. Such devices are well known to persons havingordinary skill in the art and may include those described in U.S. Pat.No. 5,423,872 which describes an implantable gastric electricalstimulator placed at the antrum area of the stomach which generatessequential electrical pulses; U.S. Pat. No. 5,690,691 for a portable orimplantable gastric pacemaker employing a number of electrodes; U.S.Pat. No. 5,836,994 for an implantable gastric stimulator whichincorporates direct sensing of the intrinsic gastric electricalactivity; U.S. Pat. No. 5,861,044 for an implantable gastric stimulatorsensing abnormal electrical activity of the gastrointestinal tract; POTApplication No. PCT/US98/10402 and U.S. patent application Ser. No.09/424,324 for an implant device equipped with tines to help secure itin the appropriate location; U.S. Pat. No. 6,041,258 for anelectrostimulation device with improved handle for laproscopic surgery;U.S. patent application Ser. No. 09/640,201 for an electrostimulationdevice attachable to enteric or endo-abdominal tissue or viscera whichis resistant to attachment; PCT Application No PCT/US00/09910 entitled“Gastric Stimulator Apparatus and Method for Installing”; PCTApplication No PCT/US00/10154 entitled “Gastric Stimulator Apparatus andMethod for Use”; U.S. patent application Ser. No. 09/713,556 entitled“Improved Process for Electrostimulation Treatment of Morbid Obesity”These devices may be altered or varied as appropriate. All Patents,Patent Applications, Provisional Patent Applications and allPublications referred to in the specification are hereby incorporated byreference.

Although the present invention is especially adapted for treatment ofobesity and/or control of weight, it may also be employed in treatmentregimes involving other stomach-related disorders including, forexample, relapsing peptic duodenal ulcer, gastric peptic disordersinduced by duodenal gastric reflux, esophageal peptic disorders inducedby gastric reflux and similar.

The method and devices used in the present invention are susceptible tonumerous modifications and variations, all of which are in the scope ofthe present inventive concept. Furthermore, all the details may bereplaced with technically-equivalent elements. Variations may be madeaccording to practices and procedures of a skilled addressee.

1. A method of increasing a tone of a patient's lower esophagealsphincter comprising: Arranging at least one stimulating electrodewithin a portion of said lower esophageal sphincter wherein saidelectrode is arranged to directly electrically stimulate the loweresophageal sphincter; and Programming a pulse generator to trigger thestimulating electrode to generate an electrical stimulation of saidlower esophageal sphincter wherein said electrical stimulation increasesthe tone of the lower esophageal sphincter.